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1. Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy

Author

Magali Michaud, Thomas Arnoux, Serena Bielli, Estelle Durand, Yann Rotrou, Sibylle Jablonka, Fabrice Robert, Marc Giraudon-Paoli, Markus Riessland, Marie-Geneviève Mattei, Emile Andriambeloson, Brunhilde Wirth, Michael Sendtner, Jorge Gallego, Rebecca M. Pruss, and Thierry Bordet

Subjects
Spinal muscular atrophy, Motor neuron disease, Mouse model, Survival motor neuron gene, Neurodegeneration, Behavior, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein leading to muscle paralysis and respiratory failure. In mouse, introducing the human SMN2 gene partially rescues Smn-/- embryonic lethality. However current models were either too severe or nearly unaffected precluding convenient drug testing for SMA. We report here new SMN2;Smn-/- lines carrying one to four copies of the human SMN2 gene. Mice carrying three SMN2 copies exhibited an intermediate phenotype with delayed appearance of motor defects and developmental breathing disorders reminiscent of those found in severe SMA patients. Although normal at birth, at 7 days of age respiratory rate was decreased and apnea frequency was increased in SMA mice in parallel with the appearance of neuromuscular junction defects in the diaphragm. With median survival of 15 days and postnatal onset of neurodegeneration, these mice could be an important tool for evaluating new therapeutics.

Published
2010
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2. Differences in the profile of protection afforded by TRO40303 and mild hypothermia in models of cardiac ischemia/reperfusion injury

Author

Renaud Tissier, Alain Berdeaux, Didier Morin, David Erlinge, Sasha Koul, Thierry Bordet, Caroline Gouarné, Thomas Arnoux, Magnus Hansson, Andrew P. Halestrap, Sophie Schaller, Osian Llwyd, Henrik Engblom, Haakan Arheden, Damien de Paulis, and Rebecca M. Pruss

Subjects
Male, Cardiotonic Agents, Swine, Ischemia, Hemodynamics, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, chemistry.chemical_compound, Hypothermia, Induced, Oximes, Animals, Secosteroids, Medicine, Respiratory function, cardiovascular diseases, Myocardial infarction, Cells, Cultured, Pharmacology, MitoQ, business.industry, Hypoxia (medical), Hypothermia, medicine.disease, Rats, chemistry, Anesthesia, cardiovascular system, Female, medicine.symptom, Reactive Oxygen Species, business, Reperfusion injury
Abstract

The mode of protection against cardiac reperfusion injury by mild hypothermia and TRO40303 was investigated in various experimental models and compared to MitoQ in vitro. In isolated cardiomyocytes subjected to hypoxia/reoxygenation, TRO40303, MitoQ and mild hypothermia delayed mPTP opening, inhibited generation of mitochondrial superoxide anions at reoxygenation and improved cell survival. Mild hypothermia, but not MitoQ and TRO40303, provided protection in a metabolic starvation model in H9c2 cells and preserved respiratory function in isolated rat heart mitochondria submitted to anoxia/reoxygenation. In the Langendorff-perfused rat heart, only mild hypothermia provided protection of hemodynamic function and reduced infarct size following ischemia/reperfusion. In biopsies from the left ventricle of pigs subjected to in vivo occlusion/reperfusion, TRO40303 specifically preserved respiratory functions in the peri-infarct zone whereas mild hypothermia preserved both the ischemic core area and the peri-infarct zones. Additionally in this pig model, only hypothermia reduced infarct size. We conclude that mild hypothermia provided protection in all models by reducing the detrimental effects of ischemia, and when initiated before occlusion, reduced subsequent reperfusion damage leading to a smaller infarct. By contrast, although TRO40303 provided similar protection to MitoQ in vitro and offered specific protection against some aspects of reperfusion injury in vivo, this was insufficient to reduce infarct size.

Published
2015

3. 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two

Author

Casey Ager, Matthew Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin Jaiswal, Michael Curran, Tina C. Albershardt, Anshika Bajaj, Jacob F. Archer, Rebecca S. Reeves, Lisa Y. Ngo, Peter Berglund, Jan ter Meulen, Caroline Denis, Hormas Ghadially, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Robert W. Wilkinson, Nicolai Wagtmann, Yannis Morel, Pascale Andre, Michael B. Atkins, Matteo S. Carlino, Antoni Ribas, John A. Thompson, Toni K. Choueiri, F. Stephen Hodi, Wen-Jen Hwu, David F. McDermott, Victoria Atkinson, Jonathan S. Cebon, Bernie Fitzharris, Michael B. Jameson, Catriona McNeil, Andrew G. Hill, Eric Mangin, Malidi Ahamadi, Marianne van Vugt, Mariëlle van Zutphen, Nageatte Ibrahim, Georgina V. Long, Robyn Gartrell, Zoe Blake, Ines Simoes, Yichun Fu, Takuro Saito, Yingzhi Qian, Yan Lu, Yvonne M. Saenger, Sadna Budhu, Olivier De Henau, Roberta Zappasodi, Kyle Schlunegger, Bruce Freimark, Jeff Hutchins, Christopher A. Barker, Jedd D. Wolchok, Taha Merghoub, Elena Burova, Omaira Allbritton, Peter Hong, Jie Dai, Jerry Pei, Matt Liu, Joel Kantrowitz, Venus Lai, William Poueymirou, Douglas MacDonald, Ella Ioffe, Markus Mohrs, William Olson, Gavin Thurston, Cristian Capasso, Federica Frascaro, Sara Carpi, Siri Tähtinen, Sara Feola, Manlio Fusciello, Karita Peltonen, Beatriz Martins, Madeleine Sjöberg, Sari Pesonen, Tuuli Ranki, Lukasz Kyruk, Erkko Ylösmäki, Vincenzo Cerullo, Fabio Cerignoli, Biao Xi, Garret Guenther, Naichen Yu, Lincoln Muir, Leyna Zhao, Yama Abassi, Víctor Cervera-Carrascón, Mikko Siurala, João Santos, Riikka Havunen, Suvi Parviainen, Akseli Hemminki, Angus Dalgleish, Satvinder Mudan, Mark DeBenedette, Ana Plachco, Alicia Gamble, Elizabeth W. Grogan, John Krisko, Irina Tcherepanova, Charles Nicolette, Pooja Dhupkar, Ling Yu, Eugenie S. Kleinerman, Nancy Gordon, Italia Grenga, Lauren Lepone, Sofia Gameiro, Karin M. Knudson, Massimo Fantini, Kwong Tsang, James Hodge, Renee Donahue, Jeffrey Schlom, Elizabeth Evans, Holm Bussler, Crystal Mallow, Christine Reilly, Sebold Torno, Maria Scrivens, Cathie Foster, Alan Howell, Leslie Balch, Alyssa Knapp, John E. Leonard, Mark Paris, Terry Fisher, Siwen Hu-Lieskovan, Ernest Smith, Maurice Zauderer, William Fogler, Marilyn Franklin, Matt Thayer, Dan Saims, John L. Magnani, Jian Gong, Michael Gray, George Fromm, Suresh de Silva, Louise Giffin, Xin Xu, Jason Rose, Taylor H. Schreiber, Sofia R. Gameiro, Paul E. Clavijo, Clint T. Allen, James W. Hodge, Kwong Y. Tsang, Jane Grogan, Nicholas Manieri, Eugene Chiang, Patrick Caplazi, Mahesh Yadav, Patrick Hagner, Hsiling Chiu, Michelle Waldman, Anke Klippel, Anjan Thakurta, Michael Pourdehnad, Anita Gandhi, Ian Henrich, Laura Quick, Rob Young, Margaret Chou, Andrew Hotson, Stephen Willingham, Po Ho, Carmen Choy, Ginna Laport, Ian McCaffery, Richard Miller, Kimberly A. Tipton, Kenneth R. Wong, Victoria Singson, Chihunt Wong, Chanty Chan, Yuanhiu Huang, Shouchun Liu, Jennifer H. Richardson, W. Michael Kavanaugh, James West, Bryan A. Irving, Ritika Jaini, Matthew Loya, Charis Eng, Melissa L. Johnson, Alex A. Adjei, Mateusz Opyrchal, Suresh Ramalingam, Pasi A. Janne, George Dominguez, Dmitry Gabrilovich, Laura de Leon, Jeannette Hasapidis, Scott J. Diede, Peter Ordentlich, Scott Cruickshank, Michael L. Meyers, Matthew D. Hellmann, Pawel Kalinski, Amer Zureikat, Robert Edwards, Ravi Muthuswamy, Nataša Obermajer, Julie Urban, Lisa H. Butterfield, William Gooding, Herbert Zeh, David Bartlett, Olga Zubkova, Larissa Agapova, Marina Kapralova, Liudmila Krasovskaia, Armen Ovsepyan, Maxim Lykov, Artem Eremeev, Vladimir Bokovanov, Olga Grigoryeva, Andrey Karpov, Sergey Ruchko, Alexandr Shuster, Danny N. Khalil, Luis Felipe Campesato, Yanyun Li, Adam S. Lazorchak, Troy D. Patterson, Yueyun Ding, Pottayil Sasikumar, Naremaddepalli Sudarshan, Nagaraj Gowda, Raghuveer Ramachandra, Dodheri Samiulla, Sanjeev Giri, Rajesh Eswarappa, Murali Ramachandra, David Tuck, Timothy Wyant, Jasmin Leshem, Xiu-fen Liu, Tapan Bera, Masaki Terabe, Birgit Bossenmaier, Gerhard Niederfellner, Yoram Reiter, Ira Pastan, Leiming Xia, Yang Xia, Yangyang Hu, Yi Wang, Yangyi Bao, Fu Dai, Shiang Huang, Elaine Hurt, Robert E. Hollingsworth, Lawrence G. Lum, Alfred E. Chang, Max S. Wicha, Qiao Li, Thomas Mace, Neil Makhijani, Erin Talbert, Gregory Young, Denis Guttridge, Darwin Conwell, Gregory B. Lesinski, Rodney JM Macedo Gonzales, Austin P. Huffman, Ximi K. Wang, Ran Reshef, Andy MacKinnon, Jason Chen, Matt Gross, Gisele Marguier, Peter Shwonek, Natalija Sotirovska, Susanne Steggerda, Francesco Parlati, Amani Makkouk, Mark K. Bennett, Ethan Emberley, Tony Huang, Weiqun Li, Silinda Neou, Alison Pan, Jing Zhang, Winter Zhang, Netonia Marshall, Thomas U. Marron, Judith Agudo, Brian Brown, Joshua Brody, Christopher McQuinn, Matthew Farren, Hannah Komar, Reena Shakya, Thomas Ludwug, Y. Maurice Morillon, Scott A. Hammond, John W. Greiner, Pulak R. Nath, Anthony L. Schwartz, Dragan Maric, David D. Roberts, Aung Naing, Kyriakos P. Papadopoulos, Karen A. Autio, Deborah J. Wong, Manish Patel, Gerald Falchook, Shubham Pant, Patrick A. Ott, Melinda Whiteside, Amita Patnaik, John Mumm, Filip Janku, Ivan Chan, Todd Bauer, Rivka Colen, Peter VanVlasselaer, Gail L. Brown, Nizar M. Tannir, Martin Oft, Jeffrey Infante, Evan Lipson, Ajay Gopal, Sattva S. Neelapu, Philippe Armand, Stephen Spurgeon, John P. Leonard, Rachel E. Sanborn, Ignacio Melero, Thomas F. Gajewski, Matthew Maurer, Serena Perna, Andres A. Gutierrez, Raphael Clynes, Priyam Mitra, Satyendra Suryawanshi, Douglas Gladstone, Margaret K. Callahan, James Crooks, Sheila Brown, Audrey Gauthier, Marc Hillairet de Boisferon, Andrew MacDonald, Laura Rosa Brunet, William T. Rothwell, Peter Bell, James M. Wilson, Fumi Sato-Kaneko, Shiyin Yao, Shannon S. Zhang, Dennis A. Carson, Cristina Guiducci, Robert L. Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Tomoko Hayashi, Ezra E. W. Cohen, David Schaer, Yanxia Li, Julie Dobkin, Michael Amatulli, Gerald Hall, Thompson Doman, Jason Manro, Frank Charles Dorsey, Lillian Sams, Rikke Holmgaard, Krishnadatt Persaud, Dale Ludwig, David Surguladze, John S. Kauh, Ruslan Novosiadly, Michael Kalos, Kyla Driscoll, Hardev Pandha, Christy Ralph, Kevin Harrington, Brendan Curti, Wallace Akerley, Sumati Gupta, Alan Melcher, David Mansfield, David R. Kaufman, Emmett Schmidt, Mark Grose, Bronwyn Davies, Roberta Karpathy, Darren Shafren, Katerina Shamalov, Cyrille Cohen, Naveen Sharma, James Allison, Tala Shekarian, Sandrine Valsesia-Wittmann, Christophe Caux, Aurelien Marabelle, Brian M. Slomovitz, Kathleen M. Moore, Hagop Youssoufian, Marshall Posner, Poonam Tewary, Alan D. Brooks, Ya-Ming Xu, Kithsiri Wijeratne, Leslie A. A. Gunatilaka, Thomas J. Sayers, John P. Vasilakos, Tesha Alston, Simon Dovedi, James Elvecrog, Iwen Grigsby, Ronald Herbst, Karen Johnson, Craig Moeckly, Stefanie Mullins, Kristen Siebenaler, Julius SternJohn, Ashenafi Tilahun, Mark A. Tomai, Katharina Vogel, Eveline E. Vietsch, Anton Wellstein, Martin Wythes, Stefano Crosignani, Joseph Tumang, Shilpa Alekar, Patrick Bingham, Sandra Cauwenberghs, Jenny Chaplin, Deepak Dalvie, Sofie Denies, Coraline De Maeseneire, JunLi Feng, Kim Frederix, Samantha Greasley, Jie Guo, James Hardwick, Stephen Kaiser, Katti Jessen, Erick Kindt, Marie-Claire Letellier, Wenlin Li, Karen Maegley, Reece Marillier, Nichol Miller, Brion Murray, Romain Pirson, Julie Preillon, Virginie Rabolli, Chad Ray, Kevin Ryan, Stephanie Scales, Jay Srirangam, Jim Solowiej, Al Stewart, Nicole Streiner, Vince Torti, Konstantinos Tsaparikos, Xianxian Zheng, Gregory Driessens, Bruno Gomes, Manfred Kraus, Chunxiao Xu, Yanping Zhang, Giorgio Kradjian, Guozhong Qin, Jin Qi, Xiaomei Xu, Bo Marelli, Huakui Yu, Wilson Guzman, Rober Tighe, Rachel Salazar, Kin-Ming Lo, Jessie English, Laszlo Radvanyi, Yan Lan, Michael Postow, Yasin Senbabaoglu, Billel Gasmi, Hong Zhong, Cailian Liu, Daniel Hirschhorhn-Cymerman, Yuanyuan Zha, Gregory Malnassy, Noreen Fulton, Jae-Hyun Park, Wendy Stock, Yusuke Nakamura, Hongtao Liu, Xiaoming Ju, Rachelle Kosoff, Kimberly Ramos, Brandon Coder, Robert Petit, Michael Princiotta, Kyle Perry, Jun Zou, Ainhoa Arina, Christian Fernandez, Wenxin Zheng, Michael A. Beckett, Helena J. Mauceri, Yang-Xin Fu, Ralph R. Weichselbaum, Whitney Lewis, Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Dongyun Wu, Jin Li, Xiaoling Liang, Xiangjun Zhou, Jinlin Hou, Raffit Hassan, Thierry Jahan, Scott J. Antonia, Hedy L. Kindler, Evan W. Alley, Somayeh Honarmand, Weiqun Liu, Meredith L. Leong, Chan C. Whiting, Nitya Nair, Amanda Enstrom, Edward E. Lemmens, Takahiro Tsujikawa, Sushil Kumar, Lisa M. Coussens, Aimee L. Murphy, Dirk G. Brockstedt, Sven D. Koch, Martin Sebastian, Christian Weiss, Martin Früh, Miklos Pless, Richard Cathomas, Wolfgang Hilbe, Georg Pall, Thomas Wehler, Jürgen Alt, Helge Bischoff, Michael Geissler, Frank Griesinger, Jens Kollmeier, Alexandros Papachristofilou, Fatma Doener, Mariola Fotin-Mleczek, Madeleine Hipp, Henoch S. Hong, Karl-Josef Kallen, Ute Klinkhardt, Claudia Stosnach, Birgit Scheel, Andreas Schroeder, Tobias Seibel, Ulrike Gnad-Vogt, Alfred Zippelius, Ha-Ram Park, Yong-Oon Ahn, Tae Min Kim, Soyeon Kim, Seulki Kim, Yu Soo Lee, Bhumsuk Keam, Dong-Wan Kim, Dae Seog Heo, Shari Pilon-Thomas, Amy Weber, Jennifer Morse, Krithika Kodumudi, Hao Liu, John Mullinax, Amod A. Sarnaik, Luke Pike, Andrew Bang, Tracy Balboni, Allison Taylor, Alexander Spektor, Tyler Wilhite, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal Aizer, Elizabeth Buchbinder, Mark Awad, Leena Ghandi, Jonathan Schoenfeld, Elizabeth Lessey-Morillon, Lisa Ridnour, Neil H. Segal, Manish Sharma, Dung T. Le, Robert L. Ferris, Andrew D. Zelenetz, Ronald Levy, Izidore S. Lossos, Caron Jacobson, Radhakrishnan Ramchandren, John Godwin, A. Dimitrios Colevas, Roland Meier, Suba Krishnan, Xuemin Gu, Jaclyn Neely, John Timmerman, Claire I. Vanpouille-Box, Silvia C. Formenti, Sandra Demaria, Erik Wennerberg, Aranzazu Mediero, Bruce N. Cronstein, Michael P. Gustafson, AriCeli DiCostanzo, Courtney Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A. Gastineau, Bruce D. Johnson, Allan B. Dietz, Cameron MacDonald, Mark Bucsek, Guanxi Qiao, Bonnie Hylander, Elizabeth Repasky, William J. Turbitt, Yitong Xu, Andrea Mastro, Connie J. Rogers, Sita Withers, Ziming Wang, Lam T. Khuat, Cordelia Dunai, Bruce R. Blazar, Dan Longo, Robert Rebhun, Steven K. Grossenbacher, Arta Monjazeb, William J. Murphy, Scott Rowlinson, Giulia Agnello, Susan Alters, David Lowe, Nicole Scharping, Ashley V. Menk, Ryan Whetstone, Xue Zeng, Greg M. Delgoffe, Patricia M. Santos, Jian Shi, Greg Delgoffe, Misako Nagasaka, Ammar Sukari, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Natalie Collins, Robert Manguso, Hans Pope, Yashaswi Shrestha, Jesse Boehm, W. Nicholas Haining, Kyle R. Cron, Ayelet Sivan, Keston Aquino-Michaels, Marco Orecchioni, Davide Bedognetti, Wouter Hendrickx, Claudia Fuoco, Filomena Spada, Francesco Sgarrella, Gianni Cesareni, Francesco Marincola, Kostas Kostarelos, Alberto Bianco, Lucia Delogu, Jessica Roelands, Sabri Boughorbel, Julie Decock, Scott Presnell, Ena Wang, Franco M. Marincola, Peter Kuppen, Michele Ceccarelli, Darawan Rinchai, Damien Chaussabel, Lance Miller, Andrew Nguyen, J. Zachary Sanborn, Charles Vaske, Shahrooz Rabizadeh, Kayvan Niazi, Steven Benz, Shashank Patel, Nicholas Restifo, James White, Sam Angiuoli, Mark Sausen, Sian Jones, Maria Sevdali, John Simmons, Victor Velculescu, Luis Diaz, Theresa Zhang, Jennifer S. Sims, Sunjay M. Barton, Angela Kadenhe-Chiweshe, Filemon Dela Cruz, Andrew T. Turk, Christopher F. Mazzeo, Andrew L. Kung, Jeffrey N. Bruce, Darrell J. Yamashiro, Eileen P. Connolly, Jason Baird, Marka Crittenden, David Friedman, Hong Xiao, Rom Leidner, Bryan Bell, Kristina Young, Michael Gough, Zhen Bian, Koby Kidder, Yuan Liu, Emily Curran, Xiufen Chen, Leticia P. Corrales, Justin Kline, Ethan G. Aguilar, Jennifer Guerriero, Alaba Sotayo, Holly Ponichtera, Alexandra Pourzia, Sara Schad, Ruben Carrasco, Suzan Lazo, Roderick Bronson, Anthony Letai, Richard S. Kornbluth, Sachin Gupta, James Termini, Elizabeth Guirado, Geoffrey W. Stone, Christina Meyer, Laura Helming, Nicholas Wilson, Robert Hofmeister, Natalie J. Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A. Fuertes Marraco, Daniel E. Speiser, Tara S. Abraham, Bo Xiang, Michael S. Magee, Scott A. Waldman, Adam E. Snook, Wojciech Blogowski, Ewa Zuba-Surma, Marta Budkowska, Daria Salata, Barbara Dolegowska, Teresa Starzynska, Leo Chan, Srinivas Somanchi, Kelsey McCulley, Dean Lee, Nico Buettner, Feng Shi, Paisley T. Myers, Stuart Curbishley, Sarah A. Penny, Lora Steadman, David Millar, Ellen Speers, Nicola Ruth, Gabriel Wong, Robert Thimme, David Adams, Mark Cobbold, Remy Thomas, Mariam Al-Muftah, Michael KK Wong, Michael Morse, Joseph I. Clark, Howard L. Kaufman, Gregory A. Daniels, Hong Hua, Tharak Rao, Janice P. Dutcher, Kai Kang, Yogen Saunthararajah, Vamsidhar Velcheti, Vikas Kumar, Firoz Anwar, Amita Verma, Zinal Chheda, Gary Kohanbash, John Sidney, Kaori Okada, Shruti Shrivastav, Diego A. Carrera, Shuming Liu, Naznin Jahan, Sabine Mueller, Ian F. Pollack, Angel M. Carcaboso, Alessandro Sette, Yafei Hou, Hideho Okada, Jessica J. Field, Weiping Zeng, Vincent FS Shih, Che-Leung Law, Peter D. Senter, Shyra J. Gardai, Nicole M. Okeley, Jennifer G. Abelin, Abu Z. Saeed, Stacy A. Malaker, Jeffrey Shabanowitz, Stephen T. Ward, Donald F. Hunt, Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas, Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Manuel Schmidt, Julian P. Sefrin, Lars Hillringhaus, Valeria Lifke, Alexander Lifke, Anna Skaletskaya, Jose Ponte, Thomas Chittenden, Yulius Setiady, Eva Sivado, Vincent Thomas, Meddy El Alaoui, Sébastien Papot, Charles Dumontet, Mike Dyson, John McCafferty, Said El Alaoui, Praveen K. Bommareddy, Andrew Zloza, Frederick Kohlhapp, Ann W. Silk, Sachin Jhawar, Tomas Paneque, Jenna Newman, Pedro Beltran, Felicia Cao, Bang-Xing Hong, Tania Rodriguez-Cruz, Xiao-Tong Song, Stephen Gottschalk, Hugo Calderon, Sam Illingworth, Alice Brown, Kerry Fisher, Len Seymour, Brian Champion, Emma Eriksson, Jessica Wenthe, Ann-Charlotte Hellström, Gabriella Paul-Wetterberg, Angelica Loskog, Ioanna Milenova, Magnus Ståhle, Justyna Jarblad-Leja, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Sharad Goyal, Ann Silk, Janice Mehnert, Nashat Gabrail, Jennifer Bryan, Daniel Medina, Leah Mitchell, Kader Yagiz, Fernando Lopez, Daniel Mendoza, Anthony Munday, Harry Gruber, Douglas Jolly, Steven Fuhrmann, Sasa Radoja, Wei Tan, Aldo Pourchet, Alan Frey, Ian Mohr, Matthew Mulvey, Robert H. I. Andtbacka, Merrick Ross, Sanjiv Agarwala, Kenneth Grossmann, Matthew Taylor, John Vetto, Rogerio Neves, Adil Daud, Hung Khong, Stephanie M. Meek, Richard Ungerleider, Scott Welden, Maki Tanaka, Matthew Williams, Sigrun Hallmeyer, Bernard Fox, Zipei Feng, Christopher Paustian, Carlo Bifulco, Sadia Zafar, Otto Hemminki, Simona Bramante, Lotta Vassilev, Hongjie Wang, Andre Lieber, Silvio Hemmi, Tanja de Gruijl, Anna Kanerva, Tameem Ansari, Srividya Sundararaman, Diana Roen, Paul Lehmann, Anja C. Bloom, Lewis H. Bender, Ian B. Walters, Jay A. Berzofsky, Fanny Chapelin, Eric T. Ahrens, Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Alexander Scholz, Danhui Zhang, Gilson Baia, Yann Chong Tan, Jeremy Sokolove, Dongkyoon Kim, Kevin Williamson, Xiaomu Chen, Jillian Colrain, Gregg Espiritu Santo, Ngan Nguyen, Wayne Volkmuth, Norman Greenberg, William Robinson, Daniel Emerling, Charles G. Drake, Daniel P. Petrylak, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Tuyen Vu, Dwayne Campogan, Heather Haynes, James B. Trager, Nadeem A. Sheikh, David I. Quinn, Peter Kirk, Murali Addepalli, Thomas Chang, Ping Zhang, Marina Konakova, Katsunobu Hagihara, Steven Pai, Laurie VanderVeen, Palakshi Obalapur, Peiwen Kuo, Phi Quach, Lawrence Fong, Deborah H. Charych, Jonathan Zalevsky, John L. Langowski, Yolanda Kirksey, Ravi Nutakki, Shalini Kolarkar, Rhoneil Pena, Ute Hoch, Stephen K. Doberstein, John Cha, Zach Mallon, Myra Perez, Amanda McDaniel, Snjezana Anand, Darrin Uecker, Richard Nuccitelli, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, Ariana N. Renrick, Menaka Thounaojam, Portia Thomas, Samuel Pellom, Anil Shanker, Duafalia Dudimah, Alan Brooks, Yu-Lin Su, Tomasz Adamus, Qifang Zhang, Sergey Nechaev, Marcin Kortylewski, Spencer Wei, Clark Anderson, Chad Tang, Jonathan Schoenhals, Efrosini Tsouko, John Heymach, Patricia de Groot, Joe Chang, Kenneth R. Hess, Adi Diab, Padmanee Sharma, David Hong, James Welsh, Andrea J. Parsons, Jardin Leleux, Stephane Ascarateil, Marie Eve Koziol, Dina Bai, Peihong Dai, Weiyi Wang, Ning Yang, Stewart Shuman, Liang Deng, Patrick Dillon, Gina Petroni, David Brenin, Kim Bullock, Walter Olson, Mark E. Smolkin, Kelly Smith, Carmel Nail, Craig L. Slingluff, Meenu Sharma, Faisal Fa’ak, Louise Janssen, Hiep Khong, Zhilan Xiao, Yared Hailemichael, Manisha Singh, Christina Vianden, Willem W. Overwijk, Andrea Facciabene, Pierini Stefano, Fang Chongyung, Stavros Rafail, Michael Nielsen, Peter Vanderslice, Darren G. Woodside, Robert V. Market, Ronald J. Biediger, Upendra K. Marathi, Kevin Hollevoet, Nick Geukens, Paul Declerck, Nathalie Joly, Laura McIntosh, Eustache Paramithiotis, Magnus Rizell, Malin Sternby, Bengt Andersson, Alex Karlsson-Parra, Rui Kuai, Lukasz Ochyl, Anna Schwendeman, James Moon, Weiwen Deng, Thomas E. Hudson, Bill Hanson, Chris S. Rae, Joel Burrill, Justin Skoble, George Katibah, Michele deVries, Peter Lauer, Thomas W. Dubensky, Xin Chen, Li Zhou, Xiubao Ren, Charu Aggarwal, Drishty Mangrolia, Roger Cohen, Gregory Weinstein, Matthew Morrow, Joshua Bauml, Kim Kraynyak, Jean Boyer, Jian Yan, Jessica Lee, Laurent Humeau, Sandra Oyola, Susan Duff, David Weiner, Zane Yang, Mark Bagarazzi, Douglas G. McNeel, Jens Eickhoff, Robert Jeraj, Mary Jane Staab, Jane Straus, Brian Rekoske, Glenn Liu, Marit Melssen, William Grosh, Nikole Varhegyi, Nadejda Galeassi, Donna H. Deacon, Elizabeth Gaughan, Maurizio Ghisoli, Minal Barve, Robert Mennel, Gladice Wallraven, Luisa Manning, Neil Senzer, John Nemunaitis, Masahiro Ogasawara, Shuichi Ota, Kaitlin M. Peace, Diane F. Hale, Timothy J. Vreeland, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Guy T. Clifton, Mark O. Hardin, Anne Toms, Na Qiao, Jennifer Litton, George E. Peoples, Elizabeth A. Mittendorf, Lila Ghamsari, Emilio Flano, Judy Jacques, Biao Liu, Jonathan Havel, Vladimir Makarov, Timothy A. Chan, Jessica B. Flechtner, John Facciponte, Stefano Ugel, Francesco De Sanctis, George Coukos, Sébastien Paris, Agnes Pottier, Laurent Levy, Bo Lu, Federica Cappuccini, Emily Pollock, Richard Bryant, Freddie Hamdy, Adrian Hill, Irina Redchenko, Hussein Sultan, Takumi Kumai, Valentyna Fesenkova, Esteban Celis, Ingrid Fernando, Claudia Palena, Justin M. David, Elizabeth Gabitzsch, Frank Jones, James L. Gulley, Mireia Uribe Herranz, Hiroshi Wada, Atsushi Shimizu, Toshihiro Osada, Satoshi Fukaya, Eiji Sasaki, Milad Abolhalaj, David Askmyr, Kristina Lundberg, Ann-Sofie Albrekt, Lennart Greiff, Malin Lindstedt, Dallas B. Flies, Tomoe Higuchi, Wojciech Ornatowski, Jaryse Harris, Sarah F. Adams, Todd Aguilera, Marjan Rafat, Laura Castellini, Hussein Shehade, Mihalis Kariolis, Dadi Jang, Rie vonEbyen, Edward Graves, Lesley Ellies, Erinn Rankin, Albert Koong, Amato Giaccia, Reham Ajina, Shangzi Wang, Jill Smith, Mariaelena Pierobon, Sandra Jablonski, Emanuel Petricoin, Louis M. Weiner, Lorcan Sherry, John Waller, Mark Anderson, Alison Bigley, Chantale Bernatchez, Cara Haymaker, Harriet Kluger, Michael Tetzlaff, Natalie Jackson, Ivan Gergel, Mary Tagliaferri, Patrick Hwu, Mario Snzol, Michael Hurwitz, Theresa Barberi, Allison Martin, Rahul Suresh, David Barakat, Sarah Harris-Bookman, Charles Drake, Alan Friedman, Sara Berkey, Stephanie Downs-Canner, Robert P. Edwards, Tyler Curiel, Kunle Odunsi, Tullia C. Bruno, Brandon Moore, Olivia Squalls, Peggy Ebner, Katherine Waugh, John Mitchell, Wilbur Franklin, Daniel Merrick, Martin McCarter, Brent Palmer, Jeffrey Kern, Dario Vignali, Jill Slansky, Anissa S. H. Chan, Xiaohong Qiu, Kathryn Fraser, Adria Jonas, Nadine Ottoson, Keith Gordon, Takashi O. Kangas, Steven Leonardo, Kathleen Ertelt, Richard Walsh, Mark Uhlik, Jeremy Graff, Nandita Bose, Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Amitabha Chaudhuri, Yu Chen, Jing Lin, Yun-bin Ye, Chun-wei Xu, Gang Chen, Zeng-qing Guo, Andrey Komarov, Alex Chenchik, Michael Makhanov, Costa Frangou, Yi Zheng, Carla Coltharp, Darryn Unfricht, Ryan Dilworth, Leticia Fridman, Linying Liu, Milind Rajopadhye, Peter Miller, Fernando Concha-Benavente, Julie Bauman, Sumita Trivedi, Raghvendra Srivastava, James Ohr, Dwight Heron, Uma Duvvuri, Seungwon Kim, Heather Torrey, Toshi Mera, Yoshiaki Okubo, Eva Vanamee, Rosemary Foster, Denise Faustman, Edward Stack, Daisuke Izaki, Kristen Beck, Dan Tong Jia, Paul Armenta, Ashley White-Stern, Douglas Marks, Bret Taback, Basil Horst, Laura Hix Glickman, David B. Kanne, Kelsey S. Gauthier, Anthony L. Desbien, Brian Francica, Justin L. Leong, Leonard Sung, Ken Metchette, Shailaja Kasibhatla, Anne Marie Pferdekamper, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, John Tallarico, Steven Bender, Chudi Ndubaku, Sarah M. McWhirter, Elena Gonzalez Gugel, Charles J. M. Bell, Adiel Munk, Luciana Muniz, Nina Bhardwaj, Fei Zhao, Kathy Evans, Christine Xiao, Alisha Holtzhausen, Brent A. Hanks, Nathalie Scholler, Catherine Yin, Pien Van der Meijs, Andrew M. Prantner, Cecile M. Krejsa, Leia Smith, Brian Johnson, Daniel Branstetter, Paul L. Stein, Juan C. Jaen, Joanne BL Tan, Ada Chen, Timothy Park, Jay P. Powers, Holly Sexton, Guifen Xu, Steve W. Young, Ulrike Schindler, Wentao Deng, David John Klinke, Hannah M. Komar, Gregory Serpa, Omar Elnaggar, Philip Hart, Carl Schmidt, Mary Dillhoff, Ming Jin, Michael C. Ostrowski, Madhuri Koti, Katrina Au, Nichole Peterson, Peter Truesdell, Gillian Reid-Schachter, Charles Graham, Andrew Craig, Julie-Ann Francis, Beatrix Kotlan, Timea Balatoni, Emil Farkas, Laszlo Toth, Mihaly Ujhelyi, Akos Savolt, Zoltan Doleschall, Szabolcs Horvath, Klara Eles, Judit Olasz, Orsolya Csuka, Miklos Kasler, Gabriella Liszkay, Eytan Barnea, Collin Blakely, Patrick Flynn, Reid Goodman, Raphael Bueno, David Sugarbaker, David Jablons, V. Courtney Broaddus, Brian West, Paul R. Kunk, Joseph M. Obeid, Kevin Winters, Patcharin Pramoonjago, Edward B. Stelow, Todd W. Bauer, Osama E. Rahma, Adam Lamble, Yoko Kosaka, Fei Huang, Kate A. Saser, Homer Adams, Christina E. Tognon, Ted Laderas, Shannon McWeeney, Marc Loriaux, Jeffery W. Tyner, Brian J. Druker, Evan F. Lind, Zhuqing Liu, Shanhong Lu, Lawrence P. Kane, Gulidanna Shayan, Julia Femel, Ryan Lane, Jamie Booth, Amanda W. Lund, Anthony Rodriguez, Victor H. Engelhard, Alessandra Metelli, Bill X. Wu, Caroline W. Fugle, Rachidi Saleh, Shaoli Sun, Jennifer Wu, Bei Liu, Zihai Li, Zachary S. Morris, Emily I. Guy, Clinton Heinze, Jasdeep Kler, Monica M. Gressett, Lauryn R. Werner, Stephen D. Gillies, Alan J. Korman, Hans Loibner, Jacquelyn A. Hank, Alexander L. Rakhmilevich, Paul M. Harari, Paul M. Sondel, Erica Huelsmann, Joseph Broucek, Dorothee Brech, Tobias Straub, Martin Irmler, Johannes Beckers, Florian Buettner, Elke Schaeffeler, Matthias Schwab, Elfriede Noessner, Alison Wolfreys, Andre Da Costa, John Silva, Andrea Crosby, Ludovicus Staelens, Graham Craggs, Annick Cauvin, Sean Mason, Alison M. Paterson, Andrew C. Lake, Caroline M. Armet, Rachel W. O’Connor, Jonathan A. Hill, Emmanuel Normant, Ammar Adam, Detlev M. Biniszkiewicz, Scott C. Chappel, Vito J. Palombella, Pamela M. Holland, Annette Becker, Manmohan R. Leleti, Eric Newcomb, Joanne B. L. Tan, Suthee Rapisuwon, Arash Radfar, Kellie Gardner, Geoffrey Gibney, Michael Atkins, Keith R. Rennier, Robert Crowder, Ping Wang, Russell K. Pachynski, Rosa M. Santana Carrero, Sarai Rivas, Figen Beceren-Braun, Scott Anthony, Kimberly S. Schluns, Deepali Sawant, Maria Chikina, Hiroshi Yano, Creg Workman, Elise Salerno, Ileana Mauldin, Donna Deacon, Sofia Shea, Joel Pinczewski, Thomas Gajewski, Stefani Spranger, Brendan Horton, Akiko Suzuki, Pamela Leland, Bharat H. Joshi, Raj K. Puri, Randy F. Sweis, Riyue Bao, Jason Luke, Marie-Nicole Theodoraki, Frances-Mary Mogundo, Haejung Won, Dayson Moreira, Chan Gao, Xingli Zhao, Priyanka Duttagupta, Jeremy Jones, Massimo D’Apuzzo, and Sumanta Pal

Subjects
0301 basic medicine, Pharmacology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Immunology, Cancer, Immunotherapy, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Family medicine, Molecular Medicine, Immunology and Allergy, Medicine, business
Abstract

O1 IL-15 primes an mTOR-regulated gene-expression program to prolong anti-tumor capacity of human natural killer cells #### Andreas Lundqvist1, Vincent van Hoef1, Xiaonan Zhang1, Erik Wennerberg2, Julie Lorent1, Kristina Witt1, Laia Masvidal Sanz1, Shuo Liang1, Shannon Murray3, Ola Larsson1

Published
2016

4. Abstract 2714: Combination of monalizumab and durvalumab as a potent immunotherapy treatment for solid human cancers

Author

Julie Lopez, Elodie Bonnet, Caroline Hoffmann, Flavien Caraguel, Vedran Brezar, Ana Ines Lalanne, Olivier Lantz, Arnaud Dujardin, Romain Remark, Clarisse Caillet, Caroline Denis, Pascale Andre, Eric Vivier, Cécile Bonnafous, Caroline Soulas, Thomas Arnoux, and Guillaume Habif

Subjects
0301 basic medicine, Cancer Research, Durvalumab, business.industry, medicine.medical_treatment, T cell, Cancer, Immunotherapy, medicine.disease, Metastasis, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Oncology, Cancer cell, Cancer research, Medicine, Monalizumab, business, CD8
Abstract

Inhibitory CD94-NKG2A (Natural Killer Group 2A) receptors are expressed on subsets of natural killer (NK) cells, γδ and CD8+ T cells. HLA-E (Human Leukocytes Antigen-E), the ligand for CD94-NKG2A, is upregulated on cancer cells of several solid tumors, providing a negative regulatory signal to tumor-infiltrating lymphocytes (TILs). Blockade of this immune checkpoint pathway with anti-NKG2A monoclonal antibodies (Ab) enhances NK cell responses to tumor cells in vitro and in humanized mice. Here, we describe NK and CD8+ T cell infiltrates in several human solid tumors by immunohistochemistry (IHC) and multicolor flow cytometry. We then studied the effects of in vitro targeting both pathways on primary human NK and CD8+ T cells. By using IHC on formalin-fixed paraffin-embedded samples on cohorts of solid tumors i.e. non-small cell lung cancer (NSCLC, n=45), stomach tumor (n=76), colorectal cancer (CRC, n=103), head and neck tumor (HNSCC, n=68), pancreatic tumors (n=77) and renal cell carcinoma (RCC, n=75), we observed NKp46+ NK cells in the large majority of cancer types (especially in RCC, HNSCC and stomach cancers). CD8+ T cells were found at significantly higher densities in all tumor types. In another cohort of HNSCC samples (n=60), higher proportions of CD94+ lymphocytes were found within the tumor islets both in the primary tumors and in the metastatic lymph nodes. In addition, in CRC patients with liver metastasis (n=101), high CD94+ cell densities were associated with poor overall survival. These data suggest that NKG2A blockade might unleash NK and T cells that are present in close contact to tumor cells. As previously shown, we confirmed that CD94-NKG2A ligand, HLA-E, was expressed by tumor cells in the large majority of solid tumor. In addition, high PD-L1 expressions were observed in NSCLC, stomach tumors, CRC and HNSCC. Flow cytometry analyses revealed that NK and CD8+ T cells co-expressing NKG2A and PD-1 were more numerous in tumor compared to matched peripheral blood and adjacent tissues of NSCLC and HNSCC patients. To mimic the “NKG2A+PD-1+” TILs phenotype, chronic stimulation of peripheral blood cells from healthy volunteers was performed using IL-15. The conditions led to the induction of NKG2A and PD-1 on NK and antigen-specific CD8+ T cell subsets. These effector cells were then co-cultured with tumor cell lines expressing HLA-E +/- PD-L1. We showed that monalizumab, a first-in class anti-NKG2A Ab, combined with durvalumab resulted in higher responses (CD107 mobilization and IFN-γ production) compared to each Ab alone. These data were confirmed in a syngeneic mouse model where both NK and CD8+ T cells were found to be involved in tumor rejection. Together, these data confirm that blocking NKG2A can potentiate the anti-tumor efficacy of PD-1 inhibitors and support the rationale for ongoing clinical trials investigating the monalizumab/durvalumab combination (NCT02671435 and NCT03088059). Citation Format: Caroline Soulas, Romain Remark, Vedran Brezar, Julie Lopez, Elodie Bonnet, Flavien Caraguel, Ana Lalanne, Caroline Hoffmann, Caroline Denis, Thomas Arnoux, Clarisse Caillet, Arnaud Dujardin, Guillaume Habif, Olivier Lantz, Cécile Bonnafous, Eric Vivier, Pascale Andre. Combination of monalizumab and durvalumab as a potent immunotherapy treatment for solid human cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2714.

Published
2018

5. Abstract 2342: NKG2A immune checkpoint blockade enhances the anti-tumor efficacy of PD1/PD-L1 inhibitors in a preclinical model

Author

Caroline Sola, Cécile Bonnafous, Nicolas Fuseri, Benjamin Rossi, Pascale Andre, Nicolai Wagtmann, Corinne Leget, Fabien Chanuc, Laurent Gauthier, Thomas Arnoux, and Yannis Morel

Subjects
0301 basic medicine, Cancer Research, biology, business.industry, Pharmacology, Immune checkpoint, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, Oncology, 030220 oncology & carcinogenesis, PD-L1, Cancer cell, biology.protein, Cancer research, Monalizumab, Medicine, Cytotoxic T cell, Antibody, business, CD8
Abstract

Monalizumab (IPH2201) is a novel, first-in-class humanized IgG4 targeting the immune checkpoint receptor NKG2A (Natural Killer Group 2A). NKG2A is expressed as a heterodimer with CD94 on the surface of subsets of cytotoxic lymphocytes: NK (Natural Killer) cells, γδ T cells and tumor infiltrating CD8 T lymphocytes. CD94/NKG2A is an inhibitory receptor that binds to HLA-E (Human Leukocyte Antigen-E) in humans and orthologous Qa-1b in mice. Upon ligand binding, CD94/NKG2A triggers inhibitory signaling that reduces NK and CD8 T cell responses. HLA-E is frequently up-regulated on cancer cells of many solid tumors or hematological malignancies, protecting from killing by NKG2A+ immune cells. By blocking the binding of CD94/NKG2A to HLA-E, monalizumab leads to enhancement of NK and cytotoxic T cell responses. The immune checkpoint receptor programmed cell death 1 (PD-1) is another inhibitory receptor widely upregulated by tumor-infiltrating T lymphocytes (TILs). In many tumor types immune surveillance is hampered by the expression of PD-L1, one of the ligands of PD-1. Blocking the PD-1 pathway has proven efficient as anti-tumor therapy. Nevertheless many patients remain refractory to these therapeutics. Combination treatment with PD-1 blockers and mAb to a second checkpoint receptor, CTLA-4, have proven effective only for some patients, suggesting a need for combining with other checkpoint blockers. The A20 cell line is a mouse B cell lymphoma line that expresses PD-L1, but not Qa-1b. Upon subcutaneous injection into Balb/c mice, A20 formed solid tumors in which PD-L1 expression was retained and where Qa-1b expression was induced. A20 tumor growth was controlled by NK and CD8 T cells. In spite of high expression of PD-1 on many immune infiltrating cells, and high expression of PD-L1 on tumor cells, monotherapy with anti-PD-1 or -PD-L1 mAb resulted in only moderate reduction in tumor growth. Interestingly, more than 50% of A20 tumor infiltrating NK cells and about 10% of CD8 T cells expressed CD94/NKG2A. The NKG2A+ CD8 T cell population also co-expressed PD-1. Qa-1b expression was induced not only on the surface of tumor cells but also on infiltrating immune cells in vivo. Consistent with the hypothesis that Qa-1b protects tumor cells from killing by NKG2A+ effector NK and T cells, treatment with an antibody that blocks NKG2A significantly delayed A20 tumor growth. Mice were then treated with both anti-NKG2A and anti-PD-1 or -PD-L1 in combination. These combinations resulted in significantly higher anti-tumor responses compared to monotherapies, characterized by an increased frequency of complete tumor cell regression. Together, these data indicate that blocking NKG2A in conjunction with PD-1/PD-L1 checkpoint inhibitors could provide synergistic anti-tumor efficacy and support the rationale for investigating this combination in clinical trials. Citation Format: Caroline Sola, Thomas Arnoux, Fabien Chanuc, Nicolas Fuseri, Benjamin Rossi, Laurent Gauthier, Corinne Leget, Cécile Bonnafous, Nicolai Wagtmann, Yannis Morel, Pascale André. NKG2A immune checkpoint blockade enhances the anti-tumor efficacy of PD1/PD-L1 inhibitors in a preclinical model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2342.

Published
2016

6. Informatisation d’une fouille : réalisation et déploiement du logiciel d’acquisition de données « FrAcTool » (Fressignes Acquisition Tool)

Author

Thomas Arnoux and Jean-Roch Houllier

Subjects
Système de Gestion de Bases de Données (SGBD), Solutréen, cartographical library, Solutrean, spatial analysis, archéométrie, Système d’Information Géographique (SIG), archeometry, OCX (OLE control), GIS (Geographical Information System), data model, topography, photographie numérique, OCX (contrôle OLE), DBMS (DataBase Management System), bibliothèque cartographique, analyse spatiale, modèle de données, topographie
Abstract

Depuis maintenant environ trois ans, une équipe pluridisciplinaire du Muséum National d’Histoire Naturelle (M.N.H.N.) travaille à l’informatisation de la fouille et de l’analyse du gisement solutréen de Fressignes (Indre, France). Cette activité pilote est également suivie dans le cadre d’un groupe de recherche, le Projet Collectif de Recherche “Préhistoire de la vallée moyenne de la Creuse”, avec pour objectifs d’étendre ses résultats à d’autres sites de la région Centre.L’été dernier, au cours de la campagne de fouilles 2000, le logiciel d’acquisition “FrAcTool” a été pour la première fois déployé et utilisé par les préhistoriens dans le cadre du relevé du matériel archéologique de Fressignes.Cet article s’attache à décrire les différentes étapes qui ont abouti à la conception et réalisation du logiciel “FrAcTool” et plus particulièrement les réflexions méthodologiques menées relativement aux problématiques d’acquisition, de gestion et d’exploitation de données archéologiques informatisées. A research team of the Muséum National d’Histoire Naturelle (M.N.H.N.) has been working for three years on the computerisation of the Fressignes solutrean site (Indre, France). This leading activity is also followed by a research project, the Projet Collectif de Recherche “Préhistoire de la vallée moyenne de la Creuse” and aims at extending its results to other sites of the Centre area.Last summer and for the first time during the 2000 campaign, the software “FrAcTool” and associated methodological process were deployed, applied on site and used by archaeologists in the context of archaeological material acquisition and management.This article focuses on the different steps that concluded with the conception and development of the software “FrAcTool”. It also puts the stress on methodological researches led relatively to the problems of acquisition, management and exploitation of computerised archaeological data.

Published
2010

7. De la transition paléolithique inférieur-moyen dans la vallée de la Garonne : l’Acheuléen supérieur de Raspide 2 (Blagnac, Haute-Garonne)

Author

Anne-Laure Berthet, David Colonge, Carole Fondeville, Thomas Arnoux, Marc Jarry, and Géraldine Delfour

Subjects
Archeology
Abstract

The Garonne valley Palaeolithic context is almost completely dominated by the middle, “ classic”, Acheulean. The discovery of an Upper Acheulean site at Raspide 2 (Blagnac, Haute-Garonne) has allowed us to improve our perception of the Palaeolithic occupation of this alluvial corridor and contributes to the documentation of the polymorphism of the transition from the Lower to the Middle Palaeolithic in south-western France. This site is original in the Toulouse area by its position on the very poorly documented lower terrace, its small size compared with the usual vast local spreads, and its industry. It associates some old characteristics – bifacial shaping and heavy cleavers – with elements clearly associated with the Middle Palaeolithic : the production of flakes is the most important, with systematization of methods known earlier (discoid, unipolar and on anvil), and the emergence of the Levallois method. Retouched tools are relatively abundant, with a Mousterian tendency. The emergence and generalization of Middle Palaeolithic technical systems have become increasingly better documented in south-western France over the past few years and Raspide 2, alongside many other sites in different occupation and resource contexts, contributes to illustrate the place occupied in the region by the Upper Acheulean., Dans un contexte garonnais largement dominé par l’Acheuléen moyen, «classique » , la découverte du gisement acheuléen supérieur de Raspide 2 à Blagnac (Haute-Garonne) complète notre perception de l’occupation paléolithique de ce couloir alluvial et contribue à documenter la polymorphie de la transition du Paléolithique inférieur au Paléolithique moyen dans le Sud-Ouest de la France. En effet, ce gisement est original dans la région toulousaine par sa position sur la basse terrasse très mal documentée, par son ampleur limitée par rapport aux vastes épandages habituels et par son industrie. Celle-ci associe des caractères anciens, façonnage bifacial et hachereau, anecdotiques, avec des éléments clairement associés au monde du Paléolithique moyen : la production d’éclats est largement prépondérante, avec une systématisation des méthodes connues antérieurement, discoïde, unipolaire et sur enclume, et l’apparition du débitage Levallois. Dans le même sens, l’outillage retouché est relativement abondant et de tendance moustérienne. L’émergence et la généralisation des systèmes techniques du Paléolithique moyen sont de mieux en mieux documentées dans le Sud-Ouest de la France ces dernières années et Raspide 2 contribue, avec de nombreux autres gisements dans des contextes d’occupations et de ressources différents, à illustrer toute la place qu’y prend l’Acheuléen supérieur., Colonge David, Jarry Marc, Delfour Géraldine, Fondeville Carole, Arnoux Thomas, Berthet Anne-Laure. De la transition paléolithique inférieur-moyen dans la vallée de la Garonne : l’Acheuléen supérieur de Raspide 2 (Blagnac, Haute-Garonne). In: Bulletin de la Société préhistorique française, tome 107, n°2, 2010. pp. 205-225.

Published
2010

8. Neuromuscular defects and breathing disorders in a new mouse model of spinal muscular atrophy

Author

Marie-Geneviève Mattei, Jorge Gallego, Serena Bielli, Rebecca M. Pruss, Emile Andriambeloson, Fabrice Robert, Magali Michaud, Yann Rotrou, Michael Sendtner, Marc Giraudon-Paoli, Markus Riessland, Thomas Arnoux, Estelle Durand, Sibylle Jablonka, Brunhilde Wirth, and Thierry Bordet

Subjects
Pathology, medicine.medical_specialty, Respiratory rate, Diaphragm, Neuromuscular Junction, Mice, Transgenic, Biology, Respiratory paralysis, Neuromuscular junction, Mouse model, lcsh:RC321-571, Muscular Atrophy, Spinal, Mice, medicine, Animals, Humans, Genetic Predisposition to Disease, Motor neuron disease, Neurodegeneration, Survival motor neuron gene, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Behavior, Spinal muscular atrophy, Anatomy, Motor neuron, medicine.disease, SMA, Neuromuscular Junction Diseases, Respiratory Paralysis, nervous system diseases, Survival of Motor Neuron 2 Protein, Disease Models, Animal, medicine.anatomical_structure, Neurology, Neuromuscular junction disease, Disease Progression, Genes, Lethal, Respiratory Insufficiency
Abstract

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein leading to muscle paralysis and respiratory failure. In mouse, introducing the human SMN2 gene partially rescues Smn(-)(/)(-) embryonic lethality. However current models were either too severe or nearly unaffected precluding convenient drug testing for SMA. We report here new SMN2;Smn(-/-) lines carrying one to four copies of the human SMN2 gene. Mice carrying three SMN2 copies exhibited an intermediate phenotype with delayed appearance of motor defects and developmental breathing disorders reminiscent of those found in severe SMA patients. Although normal at birth, at 7 days of age respiratory rate was decreased and apnea frequency was increased in SMA mice in parallel with the appearance of neuromuscular junction defects in the diaphragm. With median survival of 15 days and postnatal onset of neurodegeneration, these mice could be an important tool for evaluating new therapeutics.

Published
2009

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